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Scheibner, K. ; Schirge, S. ; Burtscher, I. ; Büttner, M. ; Sterr, M. ; Yang, D.* ; Böttcher, A. ; Ansarullah ; Irmler, M. ; Beckers, J. ; Cernilogar, F.M.* ; Schotta, G.* ; Theis, F.J. ; Lickert, H.

Epithelial cell plasticity drives endoderm formation during gastrulation.

Nat. Cell Biol. 23, 692-703 (2021)
Verlagsversion DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
It is generally accepted that epiblast cells ingress into the primitive streak by epithelial-to-mesenchymal transition (EMT) to give rise to the mesoderm; however, it is less clear how the endoderm acquires an epithelial fate. Here, we used embryonic stem cell and mouse embryo knock‐in reporter systems to combine time-resolved lineage labelling with high-resolution single-cell transcriptomics. This allowed us to resolve the morphogenetic programs that segregate the mesoderm from the endoderm germ layer. Strikingly, while the mesoderm is formed by classical EMT, the endoderm is formed independent of the key EMT transcription factor Snail1 by mechanisms of epithelial cell plasticity. Importantly, forkhead box transcription factor A2 (Foxa2) acts as an epithelial gatekeeper and EMT suppressor to shield the endoderm from undergoing a mesenchymal transition. Altogether, these results not only establish the morphogenetic details of germ layer formation, but also have broader implications for stem cell differentiation and cancer metastasis.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter To-mesenchymal Transition; Transcription Factor; Definitive Endoderm; Beta-catenin; Gene-expression; Germ Layer; E-cadherin; Mouse; Snail; Metastasis
Sprache englisch
Veröffentlichungsjahr 2021
HGF-Berichtsjahr 2021
ISSN (print) / ISBN 1465-7392
e-ISSN 1476-4679
Zeitschrift Nature Cell Biology
Quellenangaben Band: 23, Heft: 7, Seiten: 692-703 Artikelnummer: , Supplement: ,
Verlag Nature Publishing Group
Verlagsort Heidelberger Platz 3, Berlin, 14197, Germany
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes and Regeneration Research (IDR)
Institute of Computational Biology (ICB)
Institute of Experimental Genetics (IEG)
POF Topic(s) 30201 - Metabolic Health
90000 - German Center for Diabetes Research
30502 - Diabetes: Pathophysiology, Prevention and Therapy
30205 - Bioengineering and Digital Health
Forschungsfeld(er) Helmholtz Diabetes Center
Enabling and Novel Technologies
Genetics and Epidemiology
PSP-Element(e) G-502300-001
G-501900-231
A-632500-001
G-503800-001
G-500600-004
Förderungen Deutsche Forschungsgemeinschaft (German Research Foundation)
DOI 10.1038/s41556-021-00694-x
WOS ID WOS:000665784500001
Scopus ID 85108429988
PubMed ID 34168324
Erfassungsdatum 2021-07-02
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